Retreatment with a prolonged temozolomide (TMZ) dosing schedule in patients (pts) with recurrent malignant gliomas (MG)

Abstract

2078 Background: The combination of surgery, radiation and TMZ has become the standard therapy for pts with newly diagnosed MG; however, no standard has emerged for recurrent disease. Continuous dosing of TMZ for periods longer than 7 days has been shown to decrease the intratumoral concentration of the DNA repair enzyme methyl-guanine-methyl transferase and anecdotal evidence suggests that prolonged TMZ dosing has activity in pts whose tumors have progressed on standard adjuvant dosing regimens. Methods: Using an institutional neuro-oncology database, we retrospectively identified all pts with recurrent MG treated with a prolonged TMZ dosing schedule between 4/05 and 11/07. Results: Nineteen pts were identified who received prolonged TMZ dosing at recurrence at a dose of 50-100mg/m2/day for 21 consecutive days followed by 7 days off drug. All pts had received prior TMZ, 14 concurrent with and 17 following radiation. Their median age was 56 years (range 34–69) and 58% of these pts were male. Seventeen pts had glioblastoma multiforme and 2 had anaplastic astrocytomas. Seven pts had received 2 prior regimens and 2 pts had been treated with 3 prior therapies. The median number of prolonged TMZ cycles delivered was 2 (range 1–17+). Three pts were treated with concurrent tamoxifen and one received imatinib along with prolonged TMZ. Median time to progression was 9.5 weeks (range 4–112+). Only 1 brief partial response was seen while 4 pts had stable disease on last imaging. One pt remains on treatment. Hematologic toxicity included grade 3/4 lymphopenia (6 pts) and grade 3 thrombocytopenia (2 pts). No grade 3/4 anemia or neutropenia was seen. No opportunistic infections occurred. One pt had grade 3 thrombosis and transaminitis. No pt discontinued treatment due to toxicity. Conclusions: Prolonged TMZ dosing was well tolerated in pts with recurrent MG and prior TMZ treatment. Few responses were seen, but several pts exhibited prolonged disease stabilization. This data suggests a potential role for prolonged TMZ dosing, alone or in combination, in pts with recurrent MG following initial TMZ therapy. A multi-institution phase II study with correlative endpoints including assessment of MGMT inhibition is planned. No significant financial relationships to disclose.